Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

TGF-β1 polymorphisms and arterial stiffness; the Rotterdam Study

Journal of Human Hypertension volume 21, pages 431–437 (2007)Cite this article

Abstract

Arterial stiffness is a risk factor for cardiovascular disease. Transforming growth factor β1 is a pleiotropic cytokine, with many functions, including influence on the vascular wall (e.g., on angiogenesis, endothelial cells and the extracellular matrix). We investigated five functional polymorphisms in the transforming growth factor β1 gene (−800 G/A, −509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro and codon 263 Thr/Ile) in relation to arterial stiffness in a population-based study. A total of 3863 participants of the Rotterdam Study, a prospective population-based study, were included in the current study. The relations of the genotypes and haplotypes with arterial stiffness (pulse wave velocity (PWV), distensibility coefficient (DC) and pulse pressure (PP)) were studied using analyses of variance and linear regression. The analyses were adjusted for age, sex, mean arterial pressure, heart rate, conventional cardiovascular risk factors and measures of atherosclerosis. There were no associations between PWV and −800 G/A (P=0.56), −509 C/T (P=0.29), codon 10 (P=0.98) and, codon 25 (P=0.28). These polymorphisms were not associated with the DC or with PP. The haplotype-based analyses yielded similar results. The results of this study show that the TGF-β1 –800 G/A, −509 C/T, codon 10 Leu/Pro and codon 25 Arg/Pro polymorphisms are not associated with arterial stiffness.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Avolio AP, Chen SG, Wang RP, Zhang CL, Li MF, O’Rourke MF . Effects of aging on changing arterial compliance and left ventricular load in a northern Chinese urban community. Circulation 1983; 68: 50–58.

    Article  CAS  Google Scholar 

  2. Roman MJ, Saba PS, Pini R, Spitzer M, Pickering TG, Rosen S et al. Parallel cardiac and vascular adaptation in hypertension. Circulation 1992; 86: 1909–1918.

    Article  CAS  Google Scholar 

  3. Girerd X, Mourad JJ, Copie X, Moulin C, Acar C, Safar M et al. Noninvasive detection of an increased vascular mass in untreated hypertensive patients. Am J Hypertens 1994; 7: 1076–1084.

    Article  CAS  Google Scholar 

  4. London GM, Marchais SJ, Safar ME, Genest AF, Guerin AP, Metivier F et al. Aortic and large artery compliance in end-stage renal failure. Kidney Int 1990; 37: 137–142.

    Article  CAS  Google Scholar 

  5. Wada T, Kodaira K, Fujishiro K, Maie K, Tsukiyama E, Fukumoto T et al. Correlation of ultrasound-measured common carotid artery stiffness with pathological findings. Arterioscler Thromb 1994; 14: 479–482.

    Article  CAS  Google Scholar 

  6. van Popele NM, Grobbee DE, Bots ML, Asmar R, Topouchian J, Reneman RS et al. Association between arterial stiffness and atherosclerosis: the Rotterdam Study. Stroke 2001; 32: 454–460.

    Article  CAS  Google Scholar 

  7. Boutouyrie P, Tropeano AI, Asmar R, Gautier I, Benetos A, Lacolley P et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension 2002; 39: 10–15.

    Article  CAS  Google Scholar 

  8. Franklin SS, Khan SA, Wong ND, Larson MG, Levy D . Is pulse pressure useful in predicting risk for coronary heart Disease? The Framingham heart study. Circulation 1999; 100: 354–360.

    Article  CAS  Google Scholar 

  9. Mattace-Raso FU, van der Cammen TJ, Hofman A, van Popele NM, Bos ML, Schalekamp MA et al. Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study. Circulation 2006; 113: 657–663.

    Article  Google Scholar 

  10. Sayed-Tabatabaei FA, van Rijn MJ, Schut AF, Aulchenko YS, Croes EA, Zillikens MC et al. Heritability of the function and structure of the arterial wall: findings of the Erasmus Rucphen Family (ERF) study. Stroke 2005; 36: 2351–2356.

    Article  CAS  Google Scholar 

  11. Massague J . The transforming growth factor-beta family. Annu Rev Cell Biol 1990; 6: 597–641.

    Article  CAS  Google Scholar 

  12. Border WA, Noble NA . Transforming growth factor beta in tissue fibrosis. New Engl J Med 1994; 331: 1286–1292.

    Article  CAS  Google Scholar 

  13. Robertson AK, Rudling M, Zhou X, Gorelik L, Flavell RA, Hansson GK . Disruption of TGF-beta signaling in T cells accelerates atherosclerosis. J Clin Invest 2003; 112: 1342–1350.

    Article  CAS  Google Scholar 

  14. Mallat Z, Tedgui A . The role of transforming growth factor beta in atherosclerosis: novel insights and future perspectives. Curr Opin Lipidol 2002; 13: 523–529.

    Article  CAS  Google Scholar 

  15. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM et al. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A 1986; 83: 4167–4171.

    Article  CAS  Google Scholar 

  16. Grainger DJ, Metcalfe JC . A pivotal role for TGF-beta in atherogenesis? Biol Rev Camb Philos Soc 1995; 70: 571–596.

    Article  CAS  Google Scholar 

  17. Topper JN . TGF-beta in the cardiovascular system: molecular mechanisms of a context-specific growth factor. Trends Cardiovasc Med 2000; 10: 132–137.

    Article  CAS  Google Scholar 

  18. Saltis J, Agrotis A, Bobik A . Regulation and interactions of transforming growth factor-beta with cardiovascular cells: implications for development and disease. Clin Exp Pharmacol Physiol 1996; 23: 193–200.

    Article  CAS  Google Scholar 

  19. Hirschi KK, Rohovsky SA, Beck LH, Smith SR, D’Amore PA . Endothelial cells modulate the proliferation of mural cell precursors via platelet-derived growth factor-BB and heterotypic cell contact. Circ Res 1999; 84: 298–305.

    Article  CAS  Google Scholar 

  20. Hirschi KK, Rohovsky SA, D’Amore PA . PDGF, TGF-beta, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. J Cell Biol 1998; 141: 805–814.

    Article  CAS  Google Scholar 

  21. Schulick AH, Taylor AJ, Zuo W, Qiu CB, Dong G, Woodward RN et al. Overexpression of transforming growth factor beta1 in arterial endothelium causes hyperplasia, apoptosis, and cartilaginous metaplasia. Proc Natl Acad Sci USA 1998; 95: 6983–6988.

    Article  CAS  Google Scholar 

  22. Jacob T, Hingorani A, Ascher E . Overexpression of transforming growth factor-beta1 correlates with increased synthesis of nitric oxide synthase in varicose veins. J Vasc Surg 2005; 41: 523–530.

    Article  Google Scholar 

  23. Cambien F, Ricard S, Troesch A, Mallet C, Generenaz L, Evans A et al. Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure. The Etude Cas-Temoin de l’Infarctus du Myocarde (ECTIM) Study. Hypertension 1996; 28: 881–887.

    Article  CAS  Google Scholar 

  24. Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC et al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet 1999; 8: 93–97.

    Article  CAS  Google Scholar 

  25. Syrris P, Carter ND, Metcalfe JC, Kemp PR, Grainger DJ, Kaski JC et al. Transforming growth factor-beta1 gene polymorphisms and coronary artery disease. Clin Sci (London) 1998; 95: 659–667.

    Article  CAS  Google Scholar 

  26. Hofman A, Grobbee DE, de Jong PT, van den Ouweland FA . Determinants of disease and disability in the elderly: the Rotterdam Elderly Study. Eur J Epidemiol 1991; 7: 403–422.

    Article  CAS  Google Scholar 

  27. Hoeks AP, Brands PJ, Smeets FA, Reneman RS . Assessment of the distensibility of superficial arteries. Ultrasound Med Biol 1990; 16: 121–128.

    Article  CAS  Google Scholar 

  28. Kool MJ, van Merode T, Reneman RS, Hoeks AP, Struyker Boudier HA, Van Bortel LM . Evaluation of reproducibility of a vessel wall movement detector system for assessment of large artery properties. Cardiovasc Res 1994; 28: 610–614.

    Article  CAS  Google Scholar 

  29. Reneman RS, van Merode T, Hick P, Muytjens AM, Hoeks AP . Age-related changes in carotid artery wall properties in men. Ultrasound Med Biol 1986; 12: 465–471.

    Article  CAS  Google Scholar 

  30. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20: 1183–1197.

  31. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE . Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation 1997; 96: 1432–1437.

    Article  CAS  Google Scholar 

  32. Witteman JC, Grobbee DE, Valkenburg HA, van Hemert AM, Stijnen T, Burger H et al. J-shaped relation between change in diastolic blood pressure and progression of aortic atherosclerosis. Lancet 1994; 343: 504–507.

    Article  CAS  Google Scholar 

  33. Waddell TK, Dart AM, Medley TL, Cameron JD, Kingwell BA . Carotid pressure is a better predictor of coronary artery disease severity than brachial pressure. Hypertension 2001; 38: 927–931.

    Article  CAS  Google Scholar 

  34. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006; 27: 2588–2605.

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by NWO (Netherlands Organization for Scientific Research) under Grant no. 904-61-196 and under the ASPASIA Grant no. 015.000.090, by the Center for Medical Systems Biology and by the European Commission under grant QLK6-CT-2002-02629 (GENOMOS).

Author information

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands

    M P S Sie, F U S Mattace-Raso, A G Uitterlinden, A Hofman, C M van Duijn & J C M Witteman

  2. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    M P S Sie, F U S Mattace-Raso, A G Uitterlinden & P P Arp

  3. Department of Biophysics, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, The Netherlands

    A P G Hoeks

  4. Department of Physiology, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, The Netherlands

    R S Reneman

  5. Cardiovascular Institute, Paris, France

    R Asmar

Authors
  1. M P S Sie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F U S Mattace-Raso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A G Uitterlinden
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P P Arp
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Hofman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A P G Hoeks
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R S Reneman
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R Asmar
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C M van Duijn
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J C M Witteman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J C M Witteman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sie, M., Mattace-Raso, F., Uitterlinden, A. et al. TGF-β1 polymorphisms and arterial stiffness; the Rotterdam Study. J Hum Hypertens 21, 431–437 (2007). https://doi.org/10.1038/sj.jhh.1002175

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1002175

Keywords

This article is cited by

Search

Advanced search

Quick links